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The FDA approved valoctocogene roxaparvovec (Roctavian) as the first gene therapy for the treatment of adults with severe hemophilia A, drug developer Biomarin on Thursday.

Patients with severe disease are eligible for the one-time, single-dose treatment if they don't have antibodies to adeno-associated virus serotype 5 (AAV5), as detected by an FDA-approved test.

FDA approval was based on data from the global phase III , which Biomarin said is the largest phase III trial of any gene therapy in hemophilia.

"Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage," trial investigator Steven Pipe, MD, of the University of Michigan in Ann Arbor, said in a release. "The approval of Roctavian, as the first gene therapy for severe hemophilia A, has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion."

Severe hemophilia A (defined as less than 1% of normal factor VIII clotting activity) accounts for the majority of hemophilia A cases.

In its , the FDA noted that valoctocogene roxaparvovec, administered by intravenous infusion, consists of a viral vector carrying a gene for clotting factor VIII. The gene is expressed in the liver to increase factor VIII levels and reduce the risk of uncontrolled bleeding.

In the GENEr8-1 study, valoctocogene roxaparvovec reduced the average annualized bleeding rate (ABR) by 52% compared with patients' baseline ABR on routine factor VIII prophylaxis. Mean ABR among the 112 patients where baseline data was prospectively collected decreased from 5.4 to 2.6 bleeds per year over a median 3 years of follow-up.

Following gene therapy, these patients also experienced a reduction in the rate of spontaneous bleeds (from 2.3 to 0.5 bleeds/year) and joint bleeds (from 3.1 to 0.6 bleeds/year) compared to their baseline rate while receiving routine VIII prophylaxis.

Biomarin also reported that a 3-year analysis presented recently at the annual congress of the International Society on Thrombosis and Haemostasis showed an 82.9% reduction in treated bleeds, as well as a 96.8% reduction in factor VIII usage compared with baseline.

Regarding safety, the most common adverse reactions (≥5%) with valoctocogene roxaparvovec were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain.

The most common laboratory abnormalities were alanine transaminase (ALT), aspartate transaminase, lactate dehydrogenase, creatine kinase, factor VIII activity levels, gamma-glutamyl transferase, and bilirubin greater than the upper levels of normal. The majority of patients in the clinical trial required corticosteroids for ALT elevation, with a median duration of corticosteroid use of 35 weeks.

The therapy is contraindicated for patients with active infections (either acute or uncontrolled chronic), known significant hepatic fibrosis (stage 3 or 4), or cirrhosis and a known hypersensitivity to mannitol.

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